INCREASED TYROSINE PHOSPHORYLATION IN RAS TRANSFORMED FIBROBLASTS OCCURS PRIOR TO MANIFESTATION OF THE TRANSFORMED PHENOTYPE

Murine fibroblasts transformed by ras oncogenes exhibited an increased amount of tyrosine phosphorylated proteins compared to normal cells. The pattern of phosphorylation was similar to that observed in cells chronically stimulated with EGF or PDGF, and is probably due to autocrine stimulation of receptor tyrosine kinases. NIH 3T3 cells transfected with H-ras under the control of a glucocorticoid inducible promoter were used to determine the temporal relationship among expression of p21H-ras oncoprotein, increase in tyrosine phosphorylation and appearance of the transformed morphology. Enhanced tyrosine phosphorylation was observed more than 24 hours before evidence of morphological changes. These results suggest that full transformation by ras oncogenes requires cooperation with tyrosine protein kinases. © 1990.